Biological weapons, as well as naturally occurring emerging and reemerging infectious diseases, are among the greatest threats to the safety of the US population. This risk is accentuated by the fact that the category ABC priority pathogens are rarely encountered in the US in clinical settings, and as a result the level of preparedness to respond to such threats remains alarmingly low. Therefore, we are proposing to identify molecular biomarker signatures for category B pathogens by creating a consortium with investigators working in areas of the world where they are causing substantial morbidity and mortality. We will pursue an alternative and potentially complementary approach to direct pathogen detection by developing diagnostic markers based on the assessment of the host transcriptional response to infection. Indeed, we have already demonstrated that dramatic changes in blood gene expression profiles occur during the acute phase of an infection, and that those changes are pathogen-specific. In the context of this project: (1) we will collect blood samples from well characterized patients with sepsis (Burkholderia pseudomallei / Khon Kaen University, Thailand), persistent fever (Brucella sp. / Centre d'lmmunologie de Marseille Luminy, France) and diarrheal diseases (Escherichia coli, pathogenic Vibrio strains, Shigella spp, Salmonella, Campylobacter jejuni and Caliciviruses / Department of Molecular Biomedicine, CINVESTAV& Microbiology Research Laboratory at Hospital General O'Horan of Merida, Mexico); (2) we will identify candidate diagnostic signatures and indicators of disease severity for infectious diseases caused by category B priority pathogens using a genome-wide blood transcriptional screen (48,000 transcripts); and (3) we will validate candidate blood markers using a focused transcriptional assay. In summary, this program will support a productive network of investigators, including research clinicians, research scientists with expertise in the immunology and genomics fields, as well as an experience support team of bioinformaticians and biostatisticians who will work together towards the development of novel tools that will improve the management of patients with infections caused by category B priority pathogens.